1、丙泊酚在产科麻醉中应用的争议和进展,复旦大学附属妇产科医院麻醉科 黄绍强,复旦大学妇产科医院,产品说明书,孕妇及产科患者 （流产者除外）丙泊酚在孕期使用的安全性尚未证实，故本品不应用于孕期妇女 丙泊酚可通过胎盘屏障，可能会引起新生儿抑郁，因此本品不应用于产科麻醉,禁用,复旦大学妇产科医院,Miller麻醉学（第6版）,产科全麻诱导的标准：硫贲妥钠45mg/kg、司可林11.5mg/kg快速诱导 产妇低血压危机时，以氯胺酮11.5mg/kg代替硫贲妥钠,复旦大学妇产科医院,现状,丙泊酚自1986年上市后迅速在麻醉各个领域得到广泛的应用 硫贲妥钠无药？ 相当多的医院产科全麻使用丙泊酚诱导 国内外情
2、况大致相当,复旦大学妇产科医院,矛盾,该怎样来看待丙泊酚在产科麻醉中的应用？,复旦大学妇产科医院,主要内容,丙泊酚在产科病人的药代动力学 胎盘转运 丙泊酚在产科全麻中应用的评价 对新生儿的影响正反双方的证据 对子宫平滑肌的影响 在特殊产妇的应用 丙泊酚辅助椎管内麻醉的应用 清醒镇静 抗恶心呕吐 预防和处理瘙痒,复旦大学妇产科医院,丙泊酚的胎盘转运,复旦大学妇产科医院,Propofol crossed the placenta, as demonstrated by concentrations found in UVin phase 1 (0.13-0.75 g/ml ) in phase 2
3、 (0.78-1.37 g/ml ) At delivery, UV : MV0.70 +/- 0.06 for phase 1 0.76 +/- 0.10 for phase 2 UA : UV 1.09 +/- 0.04 for phase 10.70 +/- 0.05 for phase 2,Dailland P, et al. Anesthesiology. 1989;71(6):827,复旦大学妇产科医院,UA血药浓度明显低于成人丙泊酚单次诱导后再清醒的血药浓度（1.07g/ml）UA血药浓度稍高于UV血药浓度，提示胎儿组织中的丙泊酚再分布,复旦大学妇产科医院,持续输注时UA血药浓度
4、总低于UV，反映胎儿对丙泊酚的持续摄取和代谢NHP只有UA的1/10，说明药物在新生儿体内迅速代谢清除,复旦大学妇产科医院,通过乳汁摄入到新生儿体内然后作用于新生儿的药量与经胎盘作用于新生儿的药量相比可以忽略不计,复旦大学妇产科医院,丙泊酚全麻诱导 对新生儿的影响,在PubMed上检索到以英文发表在主流杂志上的RCT 11个 对Apgar评分的影响：11个RCT 对神经学和适应能力评分（NACS）的影响：7个RCT,复旦大学妇产科医院,对Apgar评分的影响,与硫贲妥钠相似： Moore J, et al. Anaesthesia. 1989, 44(9):753-7. Valtonen M,
5、 et al. Anaesthesia. 1989, 44(9):758-62. Gin T, et al. Anaesth Intensive Care. 1990, 18(2):175-9. Gregory MA, et al. Can J Anaesth. 1990, 37(5):514-20. Yau G, et al. Anaesthesia. 1991, 46(1):20-3. Siafaka I, et al. Clin Exp Obstet Gynecol. 1992, 19(2):93-6. Gin T, et al. Br J Anaesth. 1993, 70(3):31
6、1-6. Abboud TK, et al. Acta Anaesthesiol Scand. 1995, 39(2):205-9. 较硫贲妥钠低： Celleno D, et al. Br J Anaesth. 1989, 62(6):649-54. Capogna G, et al. Int J Obstet Anesth. 1991, 1(1):19-23. Celleno D, et al. J Clin Anesth. 1993, 5(4):284-8.,复旦大学妇产科医院,对Apgar评分的影响正反两方证据的比较,复旦大学妇产科医院,对NACS评分的影响,与硫贲妥钠相似： Greg
7、ory MA, et al. Can J Anaesth. 1990, 37(5):514-20. Capogna G, et al. Int J Obstet Anesth. 1991, 1(1):19-23. Gin T, et al. Br J Anaesth. 1993, 70(3):311-6. Abboud TK, et al. Acta Anaesthesiol Scand. 1995, 39(2):205-9. 较硫贲妥钠低： Celleno D, et al. Br J Anaesth. 1989, 62(6):649-54. Yau G, et al. Anaesthesi
8、a. 1991, 46(1):20-3 Celleno D, et al. J Clin Anesth. 1993, 5(4):284-8.,复旦大学妇产科医院,对NACS评分的影响正反两方证据的比较,复旦大学妇产科医院,丙泊酚药效学的评价,Compared with thiopentone propofol reduces the cardiovascular response to laryngoscopy and tracheal intubation. Maternal recovery from anesthesia may be marginally quicker. Neonat
9、al outcome is satisfactory although one group of researchers has consistently preferred thiopentone to propofol. Compared with inhalational agents infusions of propofol do not offer any significant advantages for the maintenance of anesthesia and the risk of neonatal depression is potentially greate
10、r. Although propofol has no major advantages to justify it replacing thiopentone for the induction of anesthesia in pregnancy, propofol does give satisfactory results and should be available as an alternative.,Gin T. Acta Anaesthesiol Sin. 1994，32(2):127,复旦大学妇产科医院,A controversies meeting of the Obst
11、etric Anaesthetists Association in March 2003 revealed only 25% support for the motion proposing it as the induction agent of choice. This, however, is a considerable increase from a 1997 survey of the same organization indicating that 2% admitted to having used it for Caesarean section.,Br J Anaest
12、h， 2005，94(3):393,复旦大学妇产科医院,全麻对新生儿的影响,ASA Practice Guidelines for Obstetric Anesthesia. Anesthesiology, 2007, 106: 843,复旦大学妇产科医院,异丙酚,催眠效能较硫喷妥钠强1.8倍 起效快，维持时间短，苏醒迅速 可透过胎盘，大剂量使用(用量超过2.5mg/kg)可抑制新生儿呼吸 该药说明书强调：妊娠期异丙酚除用作终止妊娠外，不宜用于产科麻醉 也有报道：异丙酚用于剖腹产有许多优点，病人迅速苏醒，未引起新生儿长时间抑制 无论用于全麻诱导或维持，很多产妇发生低血压，故应慎重,现代麻醉学（
13、第3版）,复旦大学妇产科医院,硫喷妥钠,1936年始用于产科，不影响子宫收缩，可迅速通过胎盘，但胎儿的摄取量与母体所用剂量不呈正比关系 用于妊娠期的半衰期比非妊娠期者长23倍 健康新生儿的Apgar评分与所用剂量及脐静脉血中的药物浓度无直接相关 大剂量硫喷妥钠可能抑制新生儿呼吸，故应限制剂量不超过7mg/kg 因胎儿窒息而需作急症剖腹产时由于巴比妥类药对脑似有保护作用，故仍可考虑用本药作麻醉诱导,现代麻醉学（第3版）,复旦大学妇产科医院,乙咪酯,产品说明书：慎用于产科麻醉 妊娠期间的安全性尚在研究之中，不过，在特殊情况及别无选择时，可用于孕妇 如果哺乳期必须使用本药，应终止哺乳，结束使用24h
14、后才可开始哺乳较强的肾上腺皮质功能抑制剂，用于剖宫产手术会出现新生儿皮质醇浓度下降,牛津临床麻醉学手册（第4版）,复旦大学妇产科医院,最新的指南,A rapid sequence intubation with cricoid pressure is performed with propofol, 2 to 2.5 mg/kg (reduce doses for hypovolemic or bleeding patients), and succinylcholine, 1.0 to 1.5 mg/kg, IV. Etomidate or ketamine may be used in c
15、ases of maternal hypovolemia.,Clinical anesthesia procedures of the Massachusetts general hospital. 7th ed. 2007: 552.,复旦大学妇产科医院,丙泊酚对子宫平滑肌的影响,对等长收缩的影响： Propofol concentrations of 0.5 g/ml and 2 g/ml had no significant effect on the active tension developed by muscle contraction. Propofol at concentr
16、ation of 10 g/ml reduced the active tension by 45% (P 0.02) compared with the control value. The fat emulsion had no effects on the active tension.,Shin YK, et al.Anesthesiology. 1998;89:105-9,复旦大学妇产科医院,Figure 1. An experimental recording of a uterine muscle preparation treated with Diprivan-washout
17、-Intralipid. Arrows indicate the applications of Diprivan (D) and Intralipid (I).,Shin YK, et al.Anesthesiology. 1998;89:105-9,复旦大学妇产科医院,Figure 2. An experimental recording of a uterine muscle preparation treated with Intralipid-washout-Diprivan-Oxytocin. Arrows indicate the applications of Intralip
18、id (I), Diprivan (D), and oxytocin (OT).,Shin YK, et al.Anesthesiology. 1998;89:105-9.,复旦大学妇产科医院,对等张收缩的影响：,复旦大学妇产科医院,四川大学学报(医学版) 2004 ,35 (5): 668,复旦大学妇产科医院,异丙酚临床常规应用时血药浓度一般为29 g/ml 与血浆蛋白结合率 95% 离体时游离的异丙酚0. 5 g/ml 约相当于人体内910 g/ml 的浓度,异丙酚在临床血药浓度范围内 不抑制人妊娠子宫平滑肌的收缩、不增加出血量,复旦大学妇产科医院,与瑞芬太尼联合用于剖宫产,瑞芬太尼0.5
19、 g/kg静注后以0.20 g/kg.min持续输注 以血浆浓度5 g /mL进行丙泊酚靶控输注诱导，司可林辅助插管后丙泊酚靶浓度降至2.5 g/mL 产妇的血流动力学维持非常稳定 尽管10例中有6例新生儿出现抑制，但只需简短地面罩通气即可很快恢复，无需纳洛酮和气管插管 UA pH was 7.20 in all infants.,Van de Velde M, et al. Int J Obstet Anesth. 2004,13:153,复旦大学妇产科医院,复旦大学妇产科医院,四川医学，2006 ，27 (10 )：1046,复旦大学妇产科医院,在特殊产妇的应用,Int J Obstet
20、Anesth. 2007;16(2):155. Caesarean section using total intravenous anaesthesia in a patient with Ebsteins anomaly complicated by supraventricular tachycardia. J Clin Anesth. 2004;16(3):217. Anesthesia for cesarean section in a patient with spinal muscular atrophy. Br J Anaesth. 2001;86(1):135. Use of
21、 remifentanil in a patient with peripartum cardiomyopathy requiring Caesarean section. Acta Anaesthesiol Belg. 2001;52(2):207. Target controlled infusion of remifentanil and propofol for cesarean section in a patient with multivalvular disease and severe pulmonary hypertension. J Clin Anesth. 1998;1
22、0(3):242. Propofol anesthesia for cesarean section successfully managed in a patient with moyamoya disease. Int J Obstet Anesth. 1997;6(1):59. Total intravenous anaesthesia for caesarean section in a patient with Marfans syndrome.,复旦大学妇产科医院,在这些病例报道中，新生儿抑制有的没有发生，有的发生了但比较轻微，经简单的处理很快就恢复最重要的是产妇的血流动力学维持平
23、稳，保证了这些合并严重心脑血管疾病的母亲的安全,复旦大学妇产科医院,辅助脊麻清醒镇静,Low dose propofol infusion technique (3 mg/kg/h following 0.3 mg/kg bolus) in 37 Cesarean parturients were evaluated, compared with another 33 parturients under spinal anesthesia without any sedatives. RESULTS: The induction to delivery time was 32.6 min. S
24、atisfactory conscious sedation was shown without increasing the incidence of post-spinal hypotension and hypoxemia compared with non-sedative group. The plasma propofol concentrations in the mean time of delivery in MV and UV were 0.86 and 0.33 g /ml, respectively. UV concentration neither correlate
25、d with infusion time nor exceeded the maternal venous concentration. The Apgar scores as well as UV blood gas analyses did not differ significantly between two groups.,Cheng YJ, Acta Anaesthesiol Sin. 1997 Jun;35(2):79,复旦大学妇产科医院,预防和处理 椎管内吗啡引起的瘙痒,剖宫产脊麻时0.2mg吗啡鞘内给药可以进行有效的术后镇痛，但同时会引起产妇的瘙痒 亚催眠剂量的丙泊酚（10m
26、g）能有效地处理这种副反应，但在胎儿娩出后立即静注并不能预防术后瘙痒的发生,Warwick JP, et al. Anaesthesia. 1997;52(3):270-5 Beilin Y, et al. Anesth Analg. 1998;86(2):310-3.,复旦大学妇产科医院,丙泊酚20mg能有效地预防 椎管内吗啡引起的瘙痒,复旦大学妇产科医院,Br J Anaesth. 2006 ;96(6):796,复旦大学妇产科医院,预防产妇恶心呕吐,最小有效剂量： 80 patients received either placebo or propofol at three diffe
27、rent doses immediately after clamping of the umbilical cord The rate of patients experiencing no emetic symptoms in an intraoperative, postdelivery period was 45% with propofol 0.5 mg/kg .h 80% with propofol 1.0 mg/kg .h 80% with propofol 2.0 mg/kg.h 40% with placebo,Fujii Y, et al. Obstet Gynecol.
28、2002;99:75.,复旦大学妇产科医院,丙泊酚的止吐机制,丙泊酚可增加大脑伏隔核的多巴胺浓度 早期认为止吐作用与脑内多巴胺DA2有关现认为止吐作用与丙泊酚作用于GABA受体降低极后区的5羟色胺水平有关 具有止吐作用的血药浓度为343ng/ml，负荷剂量1020mg然后再以0.6 mg/kg.h输注即可达到此浓度,Gan TJ, et al. Anesthesiology, 1997, 87:779,复旦大学妇产科医院,与其它药物比较： Prophylactic antiemetic efficacy of propofol at a subhypnotic dose (1.0 mg/kg/
29、h), droperidol 1.25 mg, and metoclopramide 10 mg is comparable in parturients undergoing cesarean delivery. Propofol at a subhypnotic dose is effective in the prevention of severe nausea. 联合用药： The combination of propofol 1.0 mg/kg/h and dexamethasone 8 mg was more effective than propofol alone for reducing the incidence of postdelivery emetic symptoms.,Numazaki M, et al. J Clin Anesth. 2003;15:423,Fujii Y, et al. Clin Ther. 2004 ;26:1286,复旦大学妇产科医院,复旦大学妇产科医院,谢谢！,
